U.S. Pat. No. 3,927,193 to Hansen et al discloses a method of tumor localization using labeled antibodies to carcinoembronic antigen (CEA), but provides examples of its use only in animals. Goldenberg et al, New Eng. J. Med., 298, 1384 (1978), reported success in clinical trials of tumor detection and localization by scintillation scanning of patients receiving radiolabeled antibodies to CEA. A special scanner subtraction technique with other radionuclides to compensate for interstitial and blood-pool background activity was considered essential for unequivocal tumor localization using that method.
However, CEA is considered to be primarily a cell-surface antigen, as reported by Heyderman, Scand. J. Immunol., 8. Suppl. 8, 119 (1978), and many others. It had been thought that tumor localization in man using injected radio-labeled tumor-associated antigens required antibodies which were specific to antigens located on the surface of the tumor cell, by Spar, Seminars In Nucl. Med., 6, 379 (1976) and Emrich, Deutsche Med. Woch., 104, 153 (1979). It is known that both human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) are cytoplasmic intracellular tumor-associated substances, Heyderman, Supra, Lee et al, Guillouzo et al, Albrechtsen et al and Ruoslahti et al, in Scand. J. Immunol., 8, Suppl. 8, pp. 485ff, 289ff, 165ff and 3ff, respectively (1978). Quinones et al, J. Nucl. Med., 12, 69 (1971) demonstrated that a human choriocarcinoma grown in hamsters could show a 2.8-fold increased uptake of radiolabeled anti-HCG antibody in the tumor as compared to that in the animals' liver. Hirai et al, Abstracts 6th Int. Res. Group for Carcinoembryonic Proteins, Marburg/Lahn, Fed. Rep. of Germany, Sept. 17-21, 1978, reported that administration of radiolabeled anti-AFP antibodies to rodents with transplanted human hepatoma, and with rat and human yolk sac tumors, revealed no "homing in" of the antibody in the tumor tissues.
Tumor radiotherapy using labeled antibodies has been suggested by many, and an indication of its success in a single multimodal therapeutic clinical use is reported by Ettinger, Cancer Treat. Rep., 63, 131 (1979). The use of boron-labeled antibodies in therapy is reported by Hawthorne et al., J. Med. Chem., 15, 449 (1972), but the combined incorporation of boron and a radioisotope for localization is not suggested.
A need continues to exist for a method of tumor detection and localization which is not confined to the use of antibodies to cell-surface antigens, which does not require repeated injection of background-compensating material for a subtraction technique, which is adaptable to both diagnosis and therapy, and which has a high reliability and a high resolution.